Clinical trials have demonstrated the efficacy of behavioral, pharmacological, and combination treatment strategies for smoking cessation, but these treatments yield frustratingly low rates of long-term abstinence. There is emerging consensus that tobacco dependence is a chronic condition, but chronic disease management models for smoking cessation are under-developed. Practitioners have scant guidance regarding how to manage cessation treatment over time. Adaptive interventions are well-suited to conditions like tobacco dependence where patients vary in response to treatment, effectiveness of treatment may change over time, and relapse is common. Sequential, multiple assignment, randomized trials (SMART) are a novel method to rigorously compare different adaptive intervention effects. We propose a SMART to identify the optimal sequence of smoking cessation treatments for smokers who respond both incompletely (any smoking after quit date) and completely to first-line treatment (8 weeks of counseling with nicotine replacement therapy), conducted in the setting of lung cancer screening programs. The U.S. Preventive Services Task Force recommendation to screen persons at high risk for lung cancer (based on age and smoking history) creates a clinical imperative to establish efficient and effective systems to trea smokers on a large scale. Our team recently demonstrated the efficacy of one adaptive intervention for smoking cessation, Tobacco Longitudinal Care (TLC), that provides counseling and nicotine replacement therapy for one year, incorporating plans for smokers who have difficulty quitting or quit and relapse. In this proposal, our primary aim is to test whether the beneficial effect of adaptive TLC treatment can be augmented by the strategic addition of pharmacist-assisted access to the prescription medications bupropion or varenicline (Medication Therapy Management). Current smokers who are eligible for lung cancer screening will be identified using the electronic medical record at the University of Minnesota and Minneapolis VA (N=1000). All participants will receive 8 weeks of evidence-based first-line smoking cessation treatment. Participants will be eligible for three potential randomizations during one year of smoking intervention: 1) to timing of identifying early response to treatment at 4 vs. 8 weeks (all participants), 2) to telephone-based tobacco longitudinal care (TLC) vs. TLC plus pharmacist-administered Medication Therapy Management (incomplete responders to first-line treatment, Primary Aim), and 3) to monthly TLC contact vs. quarterly TLC contact (complete responders to first-line treatment, Secondary Aim). The primary outcome will be 6 months of prolonged abstinence measured 18 months after the beginning of treatment. Analyses for secondary and exploratory aims will include potential moderators such as amount of response to treatment and lung cancer screening results. Results from this SMART will inform decisions regarding the intensity and sequence of smoking cessation treatments for millions of current smokers who will undergo annual low-dose CT scanning for lung cancer.